Banking Living Brain Tissue

By Manuel B. Graeber

Australia needs a repository of living brain tissue to explore the next frontier of medical research.

Today’s cultural and technological achievements are the product of the human brain. Understanding how this organ functions is widely considered the ultimate scientific frontier. Two recent “mega” science projects, unprecedented in terms of ambition and scale, reflect this appreciation.

The BRAIN Initiative (www.nih.gov/science/brain/) is funded by the US government and will focus on mapping human brain activity. The European Union’s Human Brain Project (www.humanbrainproject.eu/) has the more abstract goal of computer modelling the brain’s functions. These projects are supported by a combined research budget of about A$5 billion.

Novel and important scientific hypotheses are expected from this research. Many will require validation at the molecular, cellular and tissue levels before they can be translated into usable knowledge, diagnostic tools and treatment options. A significantly increased demand for healthy and diseased human brain tissue will ensue, including for brain tissue that is still vital.

While obtaining suitable brain material from donor autopsy cases is not at all trivial, the provision of living human brain tissue represents a most difficult area that requires specific consideration. The question of when tissue is obtained – post mortem or from the living – matters both scientifically and ethically. Patient protection needs to be absolute at all times and no tissue must be obtained without consent. Only donated post mortem and otherwise waste surgical tissue can be used.

Patients are not like consumers who have a choice. They are caught with their disease, and those who give tissue freely trust that the best possible use will be made of their gift. This trust between the donors and a tissue bank must not be breached. It is important to understand that this foundation of immaterial values distinguishes brain banks from ordinary banks.

It goes without saying that if living tissue is to be saved from disposal (e.g. during the removal of a brain tumour) this must not have an influence on the planning of the neurosurgical procedure and must not compromise the quality of the diagnostic evaluation of the tissue.

To avoid even perceived conflicts of interest, surgeons should not be the custodians of the tissue they remove. Establishing safe, long-term practices and funding is crucial as brain tissue banking needs to be built systematically and research progress can be slow.

Human brain banks have been around for a number of years but most have to struggle because funding shortages represent a constant threat. One suggested way of funding brain banks has been through close collaboration with industry – drug companies in particular – but this is not a viable option because the primary interest of a company is financial profit and not the fulfillment of a brain donor’s wishes.

However, there is nothing wrong with industry collaborations if high ethical standards are maintained. This is where charities can have an important function as mediators to prevent conflicts of interest.

Another approach to fund brain banks is through grants to researchers that enable or complement in-house research. This approach is problematic if co-authorship by brain bank staff of publications becomes a requirement for tissue users. Such pricing fundamentally interferes with a tissue collection’s core mission of maximising access for researchers – it is the opposite of what donors want.

In conclusion, it seems highly advisable to set up brain tissue repositories with public funds. Site visits by independent and internationally recognised brain tissue specialists should be organised for quality assurance purposes. Accreditation of human brain tissue collections with the International Society of Neuropathology has been suggested, and professionally trained personnel who are capable of feeding data back into the national healthcare system should be appointed to lead brain banks.

The development of a vision for brain banking by a coalition of Australian medical researchers and politicians would be a first step in establishing a national brain tissue bank that is capable of curating waste surgical material and support brain tumour research by serving as an ethically acceptable source of living human brain tissue.

Professor Manuel B. Graeber holds the Barnet-Cropper Chair of Brain Tumour Research at the Brain and Mind Research Institute, University of Sydney.

Comments

We applaud Manuel Graeber for focusing attention on the need for “Banking Living Brain Tissue”. The potential advances in health care and medical research that would come with greater investment in this enabling technology are truly immense, and we risk foregoing them to the detriment of society.

Professor Graeber’s article comes at a particularly critical moment, however, as the National Health and Medical Research Council (NHMRC) has chosen to terminate its funding of the Australian Brain Bank Network at the beginning of 2015.

While Professor Graeber focuses on tissue from patients who are alive, usually biopsy specimens are taken for primarily clinical purposes, while significant research advances have and will continue to come from banks that store nervous system tissue from well-defined patients with clearly defined disease processes.

Here the situation is different: there is a well-organised Australian Brain Bank Network with banks in Queensland, NSW, Victoria, South Australia and Western Australia (http://www.austbrainbank.org.au/) that is at current risk. “The ABBN participating brain banks collect and provide post mortem human brain tissue and related samples for research into brain and mind disorders.” Funding for this already existing national brain bank network would be the quickest way to enable additional surgical specimen collection.

The agenda that Professor Graeber espouses is already in place for brain tissue collection and research through the ABBN. The unfortunate decision by NHMRC to terminate enabling funding, however, means uncertainty for the continued existence of this Network.

The infrastructural requirements for the collection and necessary rapid use of
living brain tissue are very different from those of conventional brain banks.

What both have in common is the need for the establishment of neuropathology
as a fully developed and independent medical specialty in Australia with its
own dedicated and several year-long training program, a development that is
currently being blocked for political reasons alone (by pathologists who
prefer to do neuropathology "on the side", which is below the standard of
other developed countries - see http://www.euro-cns.org/examefn/european-fellowship-in-neuropathology/).

The infrastructural requirements for the collection of vital brain tissue for
research differ significantly from those of conventional brain banks because the
former depend on surgical rather than autopsy or research neuropathologists
who are capable of examining brain tissue for pathological changes during an
operation. Surgical neuropathologists have to be medically trained for legal
reasons alone.

Furthermore, both the collection and use of vital brain tissue will need to be
organized around brain tumor entity-focused academic neurosurgical centers
rather than whole brain collections. Those centers would be in the best
position to provide publicly funded and supervised "hotel facilities" for
world-class researchers in close vicinity to the tissue source. As an
explanation, certain brain tumor entities occur in preferred neuroanatomical
locations. In other words, collection of living brain tissue is naturally
linked to surgical neuropathology and brain tumor research rather than autopsy
neuropathology.

However, it is clear that cross talk and fertilization between the different
brain tissue specialists are much wanted and all should be supported by public
funds allowing complete independence from commercial interests for the
reason mentioned above:

The foundation of immaterial values such as lasting patient trust and support
fundamentally distinguishes brain banks from ordinary banks!

Perhaps the debate initiated on these pages of Australasian Science, which
provides a most suitable platform, can help raise government funding for the
culturally vital brain tissue banking and the introduction of an
international caliber training scheme in neuropathology to Australia, which is
an absolute requirement for advanced brain tissue banking.